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      Surveillance of duodenal adenomas in familial adenomatous polyposis patients: medical objectives and technical requirements

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      Endoscopy International Open

      © Georg Thieme Verlag KG

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          Abstract

          Patients with classical familial adenomatous polyposis (FAP) present with hundreds of colorectal adenomas requiring (sub)total colectomy at around age 20 years, and frequently duodenal adenomas. Duodenal polyposis is a progressive disease. The burden of duodenal adenomas evolves more slowly as compared to colorectal adenomas, but increases with age to the highest stage of duodenal polyposis, stage IV according to the Spigelman’s classification, with an expected cumulative frequency of 50 % at age 70 years 1. Although the surveillance recommendations are relatively clear and homogeneous in the different countries, with the first duodenal surveillance between 20 and 25 years, the modalities of treatment are much less well defined. Duodenal adenomas either ampullary or peri-ampullary present usually as flat, whitish, small lesions and slightly elevated as compared to the surrounding mucosa. There is a majority of small (< 5 mm) lesions, and some larger lesions depending on the severity of the duodenal polyposis. Endoscopists have to focus on the detection and characterization of larger (> 1 cm) lesions as these have been shown to contain foci of high-grade dysplasia in up to 50 % of cases and have been associated with a risk of cancer development.2 3 The role of the endoscopist during duodenal surveillance is to 1) detect any existing cancer (complete evaluation of the duodenum and firsts jejunal loops); and 2i) evaluate the burden of duodenal adenomas in order to estimate the risk of advanced neoplastic evolution and the adapted surveillance interval. The only available criterion nowadays is the Spigelman’s classification, which includes the number (< 10, 10 – 20, > 20), the size (< 5 mm, 5 – 10 mm, > 10 mm) and the histology (low- or high-grade dysplasia) of duodenal adenomas. Optimal endoscopic examination of the duodenum, with lateral viewing and axial viewing at the same time, using a long endoscope to visualize the proximal jejunum and indigo-carmine to improve visualization of the mucosa, although relatively consensual for expert centers, has not really been validated through prospective studies. At least, indigo-carmine dye has been shown to increase the number of adenomas detected in two series and to increase the Spigelman’s score.4 5 The question addressed in the paper by Pittayanon and colleagues 6 is that of the diagnostic value of new imaging methods (narrow band imaging and confocal microscopy) as regards the identification of duodenal adenomas. The main clinical question in this disease should be: What are the limitations of present surveillance modalities, what is the reference method of examination, and do we need new methods to improve surveillance? The main limitation of the usual surveillance of duodenal polyposis would be to overlook major neoplastic area that would evolve into cancer during the recommended surveillance interval (2 – 3 years). Some old retrospective series suggest such a limitation, but these are mainly based on a largely obsolete methodology (axial viewing, old endoscopes, no sedation) 3. In contrast, recent prospective series, even in patients with severe duodenal polyposis, do not suggest a high frequency of overlooked precancerous lesions 7. Finally, the recent progress of usual endoscopes into high-definition endoscopy will probably replace, based on our experience, even indigo-carmine dye, given the excellent visualization of even tiny adenomas. And this evolution is still underway, given the new generation of endoscopes that are under development or research. Thus, there will probably be no clinical need for new technologies to identify more duodenal adenomas in FAP patients. On the other hand, is it important to differentiate duodenal adenomas from other duodenal polyps, as proposed by Pittayanon and colleagues? There is a real concern regarding the duodenal bulb as some lesions can mimic duodenal adenomas in this area, including gastric metaplasia and Brunner glands. There is also a question regarding the identification of adenomatous tissue on the duodenal papilla, especially because biopsies, although with a very low frequency, can induce pancreatitis. In the latter case, however, it would be important to determine whether microscopic (macroscopically invisible) ampullary adenoma represent a danger for patients even on a long-term basis, given the very slow evolution of duodenal adenomas 8. In our experience, we usually leave in place small, flat, visible ampullary adenomas for years. Regarding the numerous small duodenal adenomas observed throughout the proximal and distal duodenum of patients with FAP, there is no recommendation to biopsy and thus confirm the diagnosis of adenomas, as there is almost no differential diagnosis in this area. Practically, we never take numerous biopsies of these lesions, but simply count the number of adenomas to get a satisfying evaluation of the Spigelman’s score. For these reasons, identifying exactly the nature of small whitish lesions in the proximal and distal duodenum is probably of low clinical relevance. Moreover, if this was of any clinical relevance, any new diagnostic method should be compared with simple, white-light imaging, and probably to the reference method, i.e indigo carmine dye. Finally, what is important for patients with FAP regarding duodenal examination? Three measures: 1) beginning relatively early surveillance, around age 20 years, as we observe severe polyposis in a low number of young patients; 2) following recommended modalities of examination, including anesthesia, lateral and axial viewing, examination of the proximal jejunum to identify all possible areas of advanced neoplasia; and 3) being very cautious with large (> 1 cm) adenomas, which should be removed because they represent a significant risk of high-grade dysplasia or cancer. We should keep in mind that this evaluation needs to be done at regular intervals, is time consuming, and should remain relatively simple so that gastroenterologists can keep on doing an excellent and regular evaluation of this significant risk of duodeno-jejunal cancer in patients with FAP.

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          Most cited references 8

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          Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study.

          Duodenal cancer is one of the leading causes of death in familial adenomatous polyposis (FAP) patients. An endoscopic surveillance programme was therefore initiated in 1988, the outcome of which is described in this paper. We report the 10 year follow up of 114 patients with FAP who were prospectively screened for the presence and severity of duodenal adenomas. Six of 114 patients (median age 67 years) developed duodenal adenocarcinoma. Four of these were from 11 patients who originally had Spigelman stage IV disease (advanced duodenal polyposis), which gives a 36% risk within this group of developing cancer. One case of duodenal cancer arose from 41 patients who originally had stage III disease (2%) and one cancer arose from 44 patients with original stage II disease (2%). All six patients have died: five were inoperable and one had recurrence three years after a pancreaticoduodenectomy. There was no association between duodenal cancer and site of germline mutation of the APC gene. Surveillance for duodenal adenocarcinoma and subsequent early referral for curative surgery has not been effective. Selection of patients with advanced but benign (Spigelman stage IV) duodenal polyposis for prophylactic pancreaticoduodenectomy should therefore be considered and can now be justified on the basis of these results. More comprehensive endoscopic surveillance of high risk (stage III and IV) patients is needed in an attempt to avoid underestimating the severity of duodenal polyposis, and to evaluate the role of endoscopic therapy in preventing advanced disease.
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            Surveillance of duodenal adenomas in familial adenomatous polyposis reveals high cumulative risk of advanced disease.

            The development of high-grade dysplasia (HGD) on duodenal or jejunal adenomas and of late-stage (stage IV) duodenal polyposis are major clinical events for familial adenomatous polyposis (FAP) patients. Our aim was to determine their respective frequency, risk factors, and cumulative risk. A prospective, optimized, endoscopic surveillance protocol was applied to 58 FAP patients in a university hospital. The number, size, and histology of duodenojejunal polyps were assessed, and the Spigelman's score was calculated at each endoscopy. Cox regression and linear regression analysis were used to determine risk factors for HGD development and the cumulative risk of stage IV duodenal polyposis, respectively. During a median (+/- standard deviation) follow-up of 47.9 +/- 15.6 months, 35 patients with at least two consecutive examinations had 107 duodenojejunal examinations. The Spigelman's score increased in 21 patients (60.0%), and HGD developed in 12 patients (34.2%). High initial Spigelman's score (> 7 points), but not age or APC mutation site, was a risk factor for HGD development. Estimated cumulative risk of developing stage IV duodenal polyposis was of 42.9% at age 60 (95% CI, 35.7% to 50.0%) and 50.0% at age 70 (95% CI, 42.9% to 57.1%). This prospective series shows a higher duodenal polyposis progression rate and cumulative risk of late-stage (stage IV) duodenal polyposis in FAP patients compared with previous series. These results suggest that current modalities for surveillance and management of these patients need revision.
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              High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis.

              Duodenal polyposis occurs in approximately 90 % of patients with familial adenomatous polyposis (FAP) and 5 % - 10 % develop duodenal cancer. Novel imaging techniques may improve evaluation of duodenal polyposis using the Spigelman classification. We aimed to analyze the value of high resolution endoscopy (HRE) and the additional value of chromoendoscopy in the evaluation of duodenal polyposis in FAP.
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                Author and article information

                Journal
                Endosc Int Open
                Endosc Int Open
                10.1055/s-0034-1377934
                Endoscopy International Open
                © Georg Thieme Verlag KG (Stuttgart · New York )
                2364-3722
                2196-9736
                October 2015
                08 October 2015
                : 3
                : 5
                : E456-E457
                Affiliations
                Edouard Herriot Hospital, Gastroenterology, Lyon
                Author notes
                Corresponding author Jean-Christophe Saurin Edouard Herriot Hospital Gastroenterology unit Pavillon L 2° et.Hôpital E. Herriot5 Pl d’Arsonval69437 Lyon Cedex 03France+33 4 72 11 03 69 jean-christophe.saurin@ 123456chu-lyon.fr
                10.1055/s-0034-1393130
                4612225
                © Thieme Medical Publishers
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